7. Project Summary/Abstract A current unmet clinical need is a commercial vaccine to protect at risk populations (the very young and the elderly) against Respiratory Syncytial Virus (RSV) ? a respiratory pathogen that annually in the US causes 172,000 hospitalizations and 1.5 million outpatient visits in children < 5 years old and >14,000 deaths in those over 65. The burden of this pathogen is even more pronounced in the developing world. In this Direct to Phase II project, we will further commercialize candidate live- attenuated RSV vaccine strain we have developed using our vaccine design platform, SAVE (Synthetic Attenuated Virus Engineering) (Coleman, et al. 2008 Science). SAVE is unlike any vaccine platform previously investigated ? it does not use blind serial passaging, an attenuated carrier backbone virus, or virus-like particles. SAVE utilizes genome de-optimization, and synonymous re- coding of viral ORFs to yield live-attenuated vaccine strains and has shown proof-of-concept in seven unique viruses. These designer vaccine strains are 100% antigenically identical to the wild type and present all antigens of the target virus. Our SAVE-designed RSV vaccine strains were developed in collaboration with pre-eminent RSV scientist Dr. Peter Collins of NIH-NIAID. We now have lead candidate, RSV-MinA, that is highly attenuated and shown to induce immunity in non-human primates, efficacy in Cotton Rats, and the recently demonstrated ability to neutralize human clinical RSV isolates of A and B subtypes. Furthermore, we have demonstrated genetic and phenotypic stability of MinA after serial passage. Based on our early success in primates, in August 2016 Codagenix was granted a second no fee NIAID-DMID service contract (#:VM16RDB640; PO: Kim) in support of this project to execute Process Development to develop a cGMP compliant manufacturing process for our lead RSV vaccine candidate MinA in preparation of cGMP manufacturing of clinical lots. Vaccine commercialization is a costly and multi-faceted development process that requires adherence to regulatory guidelines set by the FDA. Therefore, in this project we seek funds to support the other areas of pre-clinical development of these SAVE-designed RSV vaccine strains. These experiments include continued assaying for genetic/phenotypic stability, cGMP Master Cell Bank construction and characterization, cGMP clinical vaccine lot manufacturing, and GLP toxicology. At the end of this project, we will have produced a SAVE-RSV vaccine candidate ready for a Phase I clinical trial. The overall goal of the proposed work is to further commercialize a live-attenuated RSV vaccine that will be administered intranasally. In the initial phases of this effort (pilot data akin to a Phase I SBIR grant), Codagenix (in collaboration with Dr. Peter Collins at NIH) developed and characterized three promising RSV vaccine candidates. Efficacy, safety, and demonstration of the induction of a cross- reactive immune response has now narrowed this field of candidates to a single candidate (RSV- MinA) ready for cGMP manufacturing. We seek funds to support all other aspect of pre-clinical development to prepare this RSV vaccine for a Phase I trial.